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FDA: Background Food and Drug Administration is agency of the Department of Health and Human Services Responsible for protecting public health through regulation and supervision of food safety, tobacco products, dietary supplements, prescription and OTC pharmaceutical drugs, vaccinations, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices, cosmetics, and veterinary products The Center for Devices and Radiological Health is the branch of the FDA responsible for the premarket approval of all medical devices, as well as overseeing the manufacturing, performance, and safety of these devices.

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What is a medical device? 21 U.S.C. § 321(h): a device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is--... (1) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them, (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or (3) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.

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Once it is a medical device... Company must show that the device is substantially equivalent to one already cleared for marketing, or Company must submit an application for premarket approval

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Premarket Approval Process Most stringent type of device marketing application required by FDA Based on determination by FDA that the premarket approval contains sufficient valid scientific evidence to assure that the device is safe and effective for its intended use

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Safe and Effective FDA considers as relevant factors Persons using the device Conditions of use for the device Probable health benefit vs. injury Reliability of device

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Challenging the FDA: Legal Standard Courts may not second-guess agencies when the agencies are exercising discretion that has been granted to them by statute. A court is generally limited to asking: Whether the agency went outside the authority granted to it; Whether it followed proper procedures in reaching its decision; and Whether the decision is so clearly wrong that it must be set aside

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Review of devices under FDCA 21 U.S.C. § 321(h): a device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is--... (1) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them, (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or (3) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.

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23andme Terms of Service You understand that information you learn from 23andMe is not designed to independently diagnose, prevent, or treat any condition or disease or to ascertain the state of your health in the absence of medical and clinical information. You understand that the 23andMe services are intended for research, informational, and educational purposes only, and that while 23andMe information might point to a diagnosis or to a possible treatment, it should always be confirmed and supplemented by additional medical and clinical testing and information. You acknowledge that 23andMe urges you to seek the advice of your physician or other health care provider if you have questions or concerns arising from your Genetic Information.

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Applying Safe and Effective FDA considers as relevant factors Persons using the device Conditions of use for the device Probable health benefit vs. injury Reliability of device

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FDA warns 23andMe FDA claimed 23andMe has not provided information that its device is substantially equivalent to a legally marketed device Also claimed there was no approved application for premarket approval FDA ordered 23andMe to discontinue marketing its personal genome service

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Is it a device? Intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease health reports on 254 diseases and conditions a first step in prevention enables users to take steps toward mitigating serious diseases

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How we use medical devices What do we expect from over-the-counter devices?

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Worst case scenarios? FDA letter cites examples of false positives and false negatives BRCA-related false positive leading to prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions Assessments for drug responses carry the risks that patients relying on such tests may begin to self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome of the assessment.

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The General Problem Without proper assessment before the test, and without proper filtering and interpretation after the test, we are left with… Layperson obtaining uncorrelated (maybe unnecessary) information, and then needing to draw their own conclusions without the requisite training Strong potential for inappropriate interpretation

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1. The threat of inappropriate or harmful patient responses is overstated. most patients who discovered high risk genes consult a physician

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2. Patients have a right to weigh the risks and benefits. as long as transparency and honesty about the accuracy is achieved, allow consumers to weigh the pros and cons libertarianism vs. paternalism

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Whats next? Short term 23andmes next steps Chevron deference to FDA 1. if Congresss intent is clear then go with that 2. if not clear, goes to what agency says as long as that is a permissible construction

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Whats next? long term how to deal with genetic information Next generation sequencing--whole genome and exome sequencing Illumina sequencing platform that tests for cystic fibrosis and a universal kit for laboratories

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Questions for discussion Is a libertarian or paternalistic approach more appropriate in the personalized genomics field? What do you think is the correct resolution to this issue?